Calcitriol receptorVitanin have previously reported the cloning and sequencing of both the chicken and human vitamin Vvitamin 3 receptor cDNAs. Neurosteroid definition comparison of their deduced amino acid sequence with that rdceptor the other classic steroid hormone receptors and the receptor vitamin d steroid receptor thyroid hormone indicates that there are two regions of conservation between these molecules. The first is a 70 amino acid, cysteine-rich sequence C1the second region C2 is a 62 amino acid region located towards the carboxyl terminus of the proteins. In other systems the former has been identified as a region responsible for DNA binding activity, whereas the latter represents the NH 2 -terminal boundary of the hormone binding domain. Additionally, the vitamin D 3 receptor contains a hgh mancore reviews amino acid vitamin d steroid receptor at its carboxyl terminus C3 which exhibits homology with the receptor for thyroid hormone.
Calcitriol receptor - an overview | ScienceDirect Topics
Endocrinology of the Heart in Health and Disease, The human VDR gene, located on chromosome 12 12q The major VDR transcript is 4. VDR, like all steroid hormone receptors, is a zinc-finger transcription factor; four cysteines each tetrahedrally coordinate two zinc ions.
Vitamin D receptor VDR has been found in human skeletal muscle cells, where it affects muscle cell metabolism by binding to vitamin D metabolites. The VDR is involved in sustaining normocalcemia by inhibiting the production of parathyroid hormone and has effects on bone and skeletal muscle biology.
Almost polymorphisms are known to exist in the VDR gene location: The C allele also called F allele carriers have a three-amino acid shorter VDR than do individuals with the T allele or f allele. The shorter VDR has enhanced transactivation capacity as a transcription factor. VDR Fok I genotype was significantly related to the femoral neck bone mineral density in response to strength training, but not aerobic training. Homozygous TT genotype of the VDR gene was significantly more represented in young soccer players than in a matched sedentary population.
Boys with the TC genotype had higher total body bone mineral content and density compared to those with CC genotype. Demay, in Vitamin D Third Edition , The vitamin D receptor and its ligand play an important role in epidermal keratinocyte differentiation. In addition to promoting production of the cornified envelope, 1,25 OH 2 D and its receptor contribute to epidermal barrier formation by inducing the synthesis of lipids that are important for barrier function and by activating the innate immune system, promoting host defense to pathogen invasion.
The effect of the vitamin D receptor in these aspects of epidermal biology are largely ligand-dependent. In contrast, the actions of the vitamin D receptor that are essential for cyclic regeneration of the hair follicle do not require 1,25 OH 2 D binding. The absence of a functional vitamin D receptor leads to alopecia, a phenotype that is not observed with vitamin D deficiency or absence of CYP27B1, the enzyme required for activation of vitamin D metabolites.
Thus, the absence of receptor and the absence of ligand have different effects on the hair cycle. Vitamin D receptor VDR is expressed in the kidney, intestine, and bone in avian as well as mammalian species. In the other organs parathyroid gland, skin, pancreas, placenta, pituitary, ovary, testis, mammary gland, and heart , VDRs are also found at relatively low expression levels. VDR was purified in the early s and first cloned from chickens in VDR is a single gene product, but chicken has alternative start sites, producing two isoforms.
The DNA binding domain consists of two sets of a zinc-coordinated finger structure. The ligand-binding domain obtained by trypsin-digestion from VDR can bind 1,dihydroxyvitamin D 3 , indicating that the domain can independently achieve its function similarly to other nuclear receptors.
VDR specifically binds to 1,dihydroxyvitamin D and then forms a heterodimer with the retinoid-X receptor. The complex binds the vitamin D responsive element VDRE in target gene promoters and modulates gene expression. The VDRE in osteocalcin, osteopontin, hydroxylase genes has been well characterized and the consensus sequence consists of two imperfect repeats of AGGTCA separated by three nonspecified nucleotides .
Vitamin D receptor VDR agonists, by promoting innate immunity and regulating adaptive immune responses, behave as real immunomodulators, quite distinct from blanket immunosuppressive agents.
The exquisite anti-inflammatory, pro-tolerogenic, and immunoregulatory properties exerted by VDR agonists are the result of multiple mechanisms of actions targeting nearly all cells in the immune system, from macrophages to dendritic cells, from T to B lymphocytes. These immunoregulatory mechanisms are not only therapeutically relevant, but also represent a physiologic element in the regulation of innate and adaptive immune responses.
VDR agonists, produced by different cell types of the immune system, appear to be ideally suited for this purpose, as shown by their capacity to enhance Treg cells and promote tolerance induction. The accumulating evidence for the beneficial effects of VDR agonists represents a sound basis for a further exploration of their potential in the development of therapies for autoimmune and immune-mediated disorders. The VDR gene contains more than 25 known polymorphisms, although more than are expected based on the observed genome-wide analysis.
Single nucleotide changes producing amino acid substitutions in the DNA and ligand-binding domains are the predominant type of mutations found in the VDR gene Malloy et al. The Cdx-2 polymorphism 1e-GA is a G to A variation in a Cdx caudal-related homeodomain protein binding site in the 1e promoter region, and this site is suggested to play an important role in intestinal-specific transcription of the VDR gene, thereby influencing vitamin D-regulated calcium absorption Arai et al. AG polymorphism is located upstream of transcription start site in 1A promoter region of the VDR gene.
Several studies have associated VDR gene polymorphisms with susceptibility or resistance to various infectious and noninfectious diseases Hill, , Palma da Cunha Matta 1 , M.
Vitamin D receptors can be found in macrophages, dendritic cells, T and B lymphocytes, astrocytes, oligodendrocytes, and neurons.
Thus, it is reasonable to believe that vitamin D metabolism plays a role in most of the neuroimmunological diseases, such as MS. Many preclinical data support the use of this vitamin in MS treatment.
However, its definitive clinical benefit is yet to be confirmed. From a clinical point of view, there are also many controversies despite some nonrobust evidence of vitamin D supplementation benefits.
For example, there is some evidence that a genetically lowered 25 OH vitamin D level is associated with increased susceptibility to MS. This conclusion comes from an interesting single nucleotide polymorphism study conducted in Canada with a large cohort. Nevertheless, the authors were not able to conclude that, conversely, vitamin D sufficiency can prevent MS onset.
It binds 1,dihydroxyvitamin D 3 1,25 OH 2 -D 3 , also known as calcitriol , a hormone involved in calcium homeostasis 1. VDR is known from a relatively narrow range of species and only in vertebrates. Vitamin D receptors VDR have been found in a large number of cell types, ranging from skeletal muscle to cells important to immune and phagocytic functions e. Vitamin D increases insulin release from isolated perfused pancreatic cells.
Moreover, vitamin D metabolites can suppress immunoglobulin production by activated B-lymphocytes. T cells are also affected by vitamin D metabolites; 1, OH 2 -D 3 exhibits permissive or enhancing effects on T cell suppressor activity. A specific transport protein delivers 1, OH 2 -D 3 and other active forms of vitamin D to targeted cells.
The active form of vitamin D then interacts with receptor proteins, which in turn signals enhanced expression of selected proteins. The vitamin D-binding protein DBP , also known as group-specific component or Gc-globulin, is a multifunctional plasma protein. Because of its extensive polymorphism, DBP initially was named the group-specific component of serum, later shortened to Gc-globulin. In addition to functioning as a circulating vitamin D transport protein, it has been demonstrated to scavenge G-actin released at sites of necrotic cell death and prevents polymerization of actin in the circulation Dusso et al.
Vitamin D receptor VDR is encoded by a single gene and no isoforms have been described so far. VDR is considerably involved in the regulation of homeostatic processes. The active VDR hormone is 1,dihydroxycholecalciferol or vitamin D 3. The other vitamin D target organs, which strongly express VDR, are bone, kidney, muscle, parathyroid glands, and skin.
The crucial role of VDR in regulating bone development and calcium homeostasis is illustrated by the characteristic vitamin D deficiency diseases, such as common rickets see p. A direct involvement of VDR in bone development is also supported by the demonstration of a correlation between bone density and the existence of distinct VDR receptor alleles in the human.
Several VDR target genes have been identified, including the genes for the two bone proteins, osteocalcin and osteopontin, the calcium-binding protein calbindin D-9k, and the hydroxyvitamin D 3 hydroxylase, which is involved in vitamin D metabolism. Another type of VDR response element is that found in the osteocalcin gene, which is composed of a DR-6 motif and apparently confers vitamin D inducibility by VDR homodimers alone.
VDR has also been identified in hematolymphopoietic tissues and has been shown through vitamin D 3 to influence the differentiation of myeloid cell lineages. These observations suggest that VDR plays a role during macrophage differentiation.
Such evidence of a putative involvement of VDR in cellular differentiation is consistent with the fact that vitamin D can inhibit the growth of certain cancer cells in vitro.
Cookies are used by this site. For more information, visit the cookies page. Endocrinology of the Heart in Health and Disease, Related terms: Volume I Marie B. Demay, in Vitamin D Third Edition , The vitamin D receptor and its ligand play an important role in epidermal keratinocyte differentiation.
Volume II Luciano Adorini, in Vitamin D Third Edition , Vitamin D receptor VDR agonists, by promoting innate immunity and regulating adaptive immune responses, behave as real immunomodulators, quite distinct from blanket immunosuppressive agents.
Vitamins and the Immune System P. Orsini 2 3 , in Nutrition and Lifestyle in Neurological Autoimmune Diseases , Vitamin D Vitamin D receptors can be found in macrophages, dendritic cells, T and B lymphocytes, astrocytes, oligodendrocytes, and neurons. Species Other names Accession number References Official name: View full topic index.